An evolutionary perspective of how infection drives human genome diversity: the case of malaria

Curr Opin Immunol. 2014 Oct;30:39-47. doi: 10.1016/j.coi.2014.06.004. Epub 2014 Jul 1.


Infection with malaria parasites has imposed a strong selective pressure on the human genome, promoting the convergent evolution of a diverse range of genetic adaptations, many of which are harboured by the red blood cell, which hosts the pathogenic stage of the Plasmodium life cycle. Recent genome-wide and multi-centre association studies of severe malaria have consistently identified ATP2B4, encoding the major Ca(2+) pump of erythrocytes, as a novel resistance locus. Evidence is also accumulating that interaction occurs among resistance loci, the most recent example being negative epistasis among alpha-thalassemia and haptoglobin type 2. Finally, studies on the effect of haemoglobin S and C on parasite transmission to mosquitoes have suggested that protective variants could increase in frequency enhancing parasite fitness.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological
  • Alleles
  • Animals
  • Evolution, Molecular*
  • Genome, Human*
  • Humans
  • Malaria / epidemiology
  • Malaria / genetics*
  • Malaria / parasitology
  • Plasmodium